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Activation of the G(s) G protein-coupled receptor Rs1 in osteoblasts increases bone mineral density by 5- to 15-fold in mice and recapitulates histologic aspects of fibrous dysplasia of the bone. However, the effects of constitutive G(s) signaling on bone tissue quality are not known. The goal of this study was to determine bone tissue quality in mice resulting from osteoblast-specific constitutive G(s) activation, by the complementary techniques of FTIR spectroscopy and synchrotron radiation micro-computed tomography (SRµCT). Col1(2.3)-tTA/TetO-Rs1 double transgenic (DT) mice, which showed osteoblast-specific constitutive G(s) signaling activity by the Rs1 receptor, were created. Femora and calvariae of DT and wild-type (WT) mice (6 and 15 weeks old) were analyzed by FTIR spectroscopy. WT and DT femora (3 and 9 weeks old) were imaged by SRµCT. Mineral-to-matrix ratio was 25% lower (P = 0.010), carbonate-to-phosphate ratio was 20% higher (P = 0.025), crystallinity was 4% lower (P = 0.004), and cross-link ratio was 11% lower (P = 0.025) in 6-week DT bone. Differences persisted in 15-week animals. Quantitative SRµCT analysis revealed substantial differences in mean values and heterogeneity of tissue mineral density (TMD). TMD values were 1,156 ± 100 and 711 ± 251 mg/cm(3) (mean ± SD) in WT and DT femoral diaphyses, respectively, at 3 weeks. Similar differences were found in 9-week animals. These results demonstrate that continuous G(s) activation in murine osteoblasts leads to deposition of immature bone tissue with reduced mineralization. Our findings suggest that bone tissue quality may be an important contributor to increased fracture risk in fibrous dysplasia patients.

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We experimentally demonstrate the occurrence of negative absolute resistance (NAR) up to about -1 Omega in response to an externally applied dc current for a shunted Nb-Al/AlO_{x}-Nb Josephson junction, exposed to a microwave current at frequencies in the GHz range. The realization (or not) of NAR depends crucially on the amplitude of the applied microwave current. Theoretically, the system is described by means of the resistively and capacitively shunted junction model in terms of a moderately damped, classical Brownian particle dynamics in a one-dimensional potential. We find excellent agreement of the experimental results with numerical simulations of the model.

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BACKGROUND: Age-related defects in the development of peripheral inflammatory responses have been observed in rodents and humans. OBJECTIVE: We examined the effects of age on a centrally injected endotoxin-induced cytokine production and cellular activation in mice. METHODS: Male C57BL/6J (B6) mice, C3H/HeN mice, and C3H/HeJ mice received an intracerebroventricular injection of lipopolysaccharide (LPS) and were sacrificed at various times (2, 4, 8 h) thereafter. ELISA for IL-1beta, IL-6, IL-12, and TNF-alpha were conducted on forebrain tissue homogenates as well as plasma samples, and lectin staining to detect activated microglia was prepared for selected brain slices. RESULTS: Intracerebroventricular injection of LPS in B6 mice produced an age-associated increase in mortality which was paralleled with a significant increase in brain and plasma levels of TNF-alpha. AntiTNF-alpha- and IL-6-immunoreactive cells possessed macrophagelike morphologies and were observed along the LPS injection tract and scattered throughout the hilus of the dorsal hippocampus and cerebral cortices. This LPS-mediated response was found to be specific in that the LPS-hyporesponsive mouse strain (C3H/HeJ) failed to demonstrate significant brain or plasma levels of TNF-alpha after LPS administration compared to C3H/HeN mice. CONCLUSION: These results suggest that the age-related increases in TNF-alpha production and mortality following the intracerebroventricular administration of LPS may be due to an increased endotoxin hypersensitivity of brain microglia/macrophages within aged animals.

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Traditional beliefs about regression to the mean, difference scores (d-scores) and corrections for regression in determining the significance of individual person change have been challenged by proponents of growth curve modeling for the study of change. These challenges have generally not been adequately addressed by those proposing modifications to Jacobson's Reliable Change Index (RC). It is proposed that (1) two-wave designs and RC or variations of it are not very good methods for the scientific study of change, (2) multi-wave designs are better, (3) d-scores are unbiased data for analyzing two-wave studies, (4) RC is relatively more justifiable than most corrected or adjusted forms of RC, (5) the more appropriate place for two-wave designs and RC are in program or outcome evaluation and (6) the most appropriate function for RC is to facilitate communication among evaluators, public decision makers, providers and the public. In the absence of a 'gold standard' or consensus, it is recommended the only RC be used in outcome evaluation, in the near future, in order to enhance comparability of change rate data among different studies.

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Mean cell volume (MCV) of erythrocytes has been reported to increase with age in humans, and to be negatively correlated with memory performance in humans and rats. We evaluated hematological changes in 21-mo old male Fischer 344 rats undergoing a 3-mo twice weekly subcutaneous injection of human recombinant erythropoietin (EPO). A baseline hematocrit (HCT) was obtained initially and repeated at monthly intervals to determine the effectiveness of EPO treatment. At 24-mo of age and after 3 mo EPO treatment, the rats were tested for their ability to learn a 14-unit T maze. Following maze testing, blood was drawn for hematologic analyses, including HCT, MCV, maximum swollen cell volume (MCVS), mean cell transit time (MCTT), and the membrane shear modulus of elasticity (G), the latter a derived measure of the relative elasticity of the red cell membrane. After 1 mo EPO treatment, HCT significantly increased compared to saline-injected controls. After 2 mo treatment, HCT began to decline but remained elevated above baseline levels even after 3 mo treatment. After 3 mo EPO treatment, MCV was significantly lower in EPO-treated rats compared to controls. These changes imply altered hemopoiesis to produce cells which undergo shrinkage associated with accelerated cellular aging. The lower MCV would have predicted a shorter MCTT which instead was unchanged. This observation suggested the presence of an additional factor contributing to the MCTT. The G, which measures the membrane contribution to deformability, very significantly increased with EPO treatment. This finding indicates an increased contribution of membrane properties to the MCTT after EPO treatment, which cancels the expected decrease in MCTT for smaller cells. After 3 mo of EPO treatment, aged rats exhibited significantly impaired maze learning compared to controls. A relationship between, changes in erythrocyte membrane properties and impaired function was indicated by a significant correlation (r=0.67, p <0.04) between G and errors in the 14-unit T-maze. These findings suggest that stress-induced erythropoiesis produces accelerated aging in the red blood cell population that may have functional implications (i.e., impaired learning ability).

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Although the prevalence of AIDS among middle and older adults is increasing, little is known about them. The objective of this study was to obtain basic demographic and social information about people with HIV/AIDS (PWAs) over the age of 44 years. This was a descriptive, cross-sectional survey of convenience samples of 76 African-American (AA) and 80 White older PWAs. Participants were interviewed by trained peer interviewers using a structured and largely objective schedule. Participants and interviewers were each paid $35 per completed interview. The schedule consisted of wide-ranging demographic, HIV/AIDS, stressor, coping, social, and support questions. Although both ethnic groups had incomes significantly below national norms and poverty rates three times their national rates, AA PWAs were markedly disadvanted socioeconomically relative to White PWAs. Although over 60% of all PWAs reported that having enough money to live on was a problem, AAs also reported significantly more Stressors, many related to economics, then White PWAs. AA PWAs reported being predominantly heterosexual, while the largest group of Whites was homosexual or bisexual. Sources of infection paralleled sexual orientation. Both groups used relatively effective coping strategies and reported moderate levels of social support and activity. It was concluded that the course of illness, treatment, and quality of life of middle and older PWAs are likely to be complicated by economic factors, and this will be particularly serious among AA PWAs.

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Calorie restriction (CR), undernutrition without malnutrition, extends the mean and maximal lifespan of several ecologically diverse species. Rodents on CR demonstrate increased activity measured as spontaneous locomotion, wheel running, open field behavior or movement. Activity measures were recorded from 19 male rhesus monkeys (Macaca mulatta) as either controls (C) which were fed a nutritious diet to approximate ad libitum levels, or as experimentals (E) which were fed 30% less than age- and weight-matched controls. Within each diet group, some monkeys (n = 10) began CR at 2.3 years of age (range 2.2-2.4 yrs, J Group) while another group (n = 9) began CR at approximately 4.6 years of age (range 4-5.25, A group). Beginning about 6 years after initiation of the study, behavioral activity was measured via ultrasonic motion detectors and recorded on videotape. Diurnal and circadian activity was clearly discernible. Peaks in activity were associated with mealtime and colony husbandry. Compared to Group A, Group J monkeys exhibited higher overall activity as measured by sensors, and also significantly more circling. Compared to AC monkeys, group AE monkeys demonstrated higher rates of gross motor behavior, pacing, stereotypies and grooming. The increases in motor activity observed in one group of monkeys were consistent with results obtained from rodent studies of CR and aging. CR did not significantly inhibit or negatively influence the display of behavior of rhesus monkeys in the laboratory environment. We report here, for the first time, increases in activity due to CR in a model other than the rodent.

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Male Mongolian gerbils (Meriones unguiculatus) 14-54 months old (n = 77) were evaluated in a battery of psychomotor (open field, locomotor, and runwheel activity, rotorod performance) and learning (one-way active avoidance in a straight runway and in 14-unit T-maze performance) tests. Body weight and seizure activity were also monitored. According to linear regression analysis, runwheel activity decreased with age; and the number of errors in the 14-unit T-maze increased as a function of age (ps < 0.05). None of the other behavioral measures or body weight were significantly correlated with age. This gerbil strain (Tumblebrook Farms; West Brookfield, MA) tended to be very prone to seizures with 64% of the gerbils experiencing at least one seizure while being tested. Seizures tended to occur when the gerbil was exposed to a novel situation (e.g., initial weighing, placement on the rotorod). An age-related decline in some aspects of psychomotor and learning performance was observed, suggesting the gerbil as an additional mammalian model of aging. The high incidence of seizure activity presented a complicating and confounding variable to the interpretation of the results of the behavioral tests used in the present study. Interventions to control seizure activity (e.g., systematic, controlled breeding; adaptation to apparati) in this model will likely increase its viability as a mammalian model of aging.

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Interest has been renewed in methods for determining individual client change. Currently, there are at least 4 pretreatment-posttreatment (pre-post) difference score methods. A 5th method, based on a random effects model and multiwave data, represents a growth curve approach and was hypothesized to be more sensitive to detecting significant (p < .05) change than the pre-post methods. The change rates produced by the 5 methods were compared in a sample of 73 older outpatients with 3 to 5 assessments per client on a measure of well-being (H. J. Dupuy, 1977). Results indicated that the growth curve approach improvement rate was the highest (68.5%). The growth curve and the Edwards-Nunnally (63.0%) methods produced significantly (p < .05) higher improvement rates than the other 3 methods, with 1 exception.

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A new generation of cholinesterase inhibitors is expected to overcome some limitations of the therapeutic use of anticholinesterases. Phenserine is a long-acting and selective inhibitor of acetylcholinesterase with a preferential brain uptake. We have assessed the effects of chronic phenserine tartrate treatment on performance of aged Fischer-344 rats in the 14-unit T-maze. Phenserine (1-3 mg kg-1, i.p.) treatment for 5 days significantly reduced the number of errors made in the Stone maze. Other performance variables were also improved. No side effects were noted across 5 days treatment at doses of 1-2 mg kg-1. Phenserine can therefore improve the performance of aged rats in this complex maze task without producing obvious side effects.

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This study investigated the hypothesis that the greater the predeath length of stay in hospice the better would be the primary caregivers' bereavement adjustment 6 months post death. One hundred sixty caregivers from a 30% pool of hospice survivors who voluntarily returned 6-month, follow-up questionnaires were studied. Five length of stay groups were compared. There were no statistically significant differences in bereavement adjustment between caregivers with varying predeath lengths of stay. It was concluded that bereavement resolution is a complex process, and that cumulative medical illness burden, impairment of ADLs, and caregiver burden need to be considered.

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Outcome research does not seem to have informed policymakers, decision makers, or practitioners. It is proposed that reporting of improvement-deterioration rates and greater use of single-sample, pretreatment-posttreatment designs in community clinic settings will facilitate communication and, perhaps, mitigate the external validity problem of psychotherapy experiments. The Edwards-Nunnally method (D. C. Speer, 1992) was used to investigate change rates from a single cohort of older adult outpatients (N = 92). The cohort improvement rate was 51%, and the deterioration rate was 5%. However, improvement rates for clients with major depression and adjustment disorders were greater than 70%. Change rates of student and staff therapists and of clients treated in the clinic and in their homes were not significantly different. Deteriorated clients are briefly described.

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ACL substitutes made of braided or plied purified collagen fibers and cross-linked with hexamethylenediisocyanate were implanted into a total of 14 adult goats to achieve resorption within 8 to 10 months. Two types of collagen fiber prostheses differing in degree of collagen purification were tested. The implants were harvested 2 to 11 months postimplantation, tested for mechanical strength, and evaluated by morphological methods. In the first group (n = 5), the less purified and less cross-linked collagen fiber ACL implant induced fast connective tissue ingrowth. At 6 months postimplantation, 40 to 60% of the collagen implant was resorbed. No studies on breaking strength were done in this group. In the second group, highly purified and more crosslinked ACL implants were less infiltrated by cells and were resorbed only by 10 to 20%. Still, the breaking strength was decreased to 10% of the original implant strength. In the second group, the fixation of the ACL implant in the bone tunnel with a bone wedge was insufficient (n = 6); however, additional fixation with metal screws was successful (n = 3). We conclude that cross-linked collagen fibers alone cannot be used as a safe ACL substitute as they quickly lose mechanical strength despite limited biodegradation.

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OBJECTIVE: To investigate the rate and configurations of current comorbid mental and substance disorders among older psychiatric patients. DESIGN: A descriptive, retrospective study. SETTING: A non-acute, public residential psychiatric treatment facility for adults 55 years of age and older (mean length of stay: 3 months). PATIENTS: 128 patients discharged during a 2-year period. MEASURES: DSM-III-R diagnoses, demographic and history data. RESULTS: The overall prevalence rate of concurrent mental and substance disorders during the present treatment episode was 21%. This is comparable to the 6-month rate of 19.8% found in the Epidemiological Catchment Area Study among adults in treatment (all ages). Nearly 50% of the dually diagnosed subsample received more than two diagnoses, with 60% of the subsample receiving a personality disorder diagnosis. Concurrent affective, alcohol, and personality disorder diagnoses were common. CONCLUSION: Older patients with comorbid substance-use and mental disorders may differ substantively from comorbid younger patients. Among older patients in an intermediate-term psychiatric facility, the triple occurrence of alcoholism personality disorder and depression was common.

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The relationship between statistically and clinically significant change has been enigmatic. Jacobson and Truax (1991) have proposed an important step toward rapprochement. However, their suggested index of clinically significant change neglects possible confounding of improvement rate estimates by regression to the mean. An alternative method is described that incorporates an adjustment that minimizes this confounding when statistical regression has been shown to be present. If regression is not present, the Jacobson and Truax method is more appropriate; if regression is present, the Edwards-Nunnally method (Edwards, Yarvis, Mueller, Zingale, & Wagman, 1978) is more appropriate. The two methods are compared, and the effects of instrument reliability and sample deviance on estimated improvement rates are demonstrated using general well-being test-retest data from a sample of older adult mental health outpatients.

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Differences in demographic and social characteristics and treatment history of 407 patients age 55 or older were examined in relation to diagnosis. Seven diagnostic groups in three mental health service programs were studied, all of which were characterized by surprisingly high rates of previous treatment (75 percent overall). Patients in the dysthymia, adjustment disorder, and V code groups appeared to be the most similar and to have the greatest psychosocial resources and fewest indicators of chronicity. Schizophrenic and bipolar patients had the least resources and most indicators of chronicity. Substance abuse patients tended to live alone, while those with major depression seemed to have more resources and later onset of their illness than schizophrenic and bipolar patients. About half of those with milder diagnoses had received prior outpatient treatment, suggesting that perhaps past treatment success leads older adults to revisit mental health services.

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Descriptive demographic, clinical and interview data from clients of an outpatient mental health clinic for older adults are presented. These clients are better educated and have a more frequent history of marital difficulties than older adults in general. Although a significant minority received V code and Adjustment Disorder diagnoses, the majority were depressed and had histories of prior mental health services. Economic factors are a major issue in seeking services.

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Case finding and successfully engaging and treating older adults with substance abuse disorders continue to be enigmatic processes. Because of the adverse consequences on health of substance abuse among the elderly, substance abuse has serious implications not only for the well-being of the elderly but also for the future costs and resources of the mental health and health care systems for older adults. However, older adults with concurrent mental and substance abuse disorders are appearing in the public gerontological mental health system. This system is both unprepared and ill-equipped to manage and treat these often difficult clients. Further complicating the situation is the seeming lack of knowledge about "dual diagnosis" among the elderly. Policy and planning issues necessary to address this newly discovered array of problems are discussed.

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Imaging is basic in the orthopedic evaluation of hip disorders. For optimal evaluation of these images, the orthopedic surgeon must not only correlate normal anatomy and pathology with radiographic findings, but must also be familiar with the newer modalities of CT, magnetic resonance imaging and ultrasound and the role and place of these studies in the evaluation of musculoskeletal disorders. This article correlates normal anatomy of the hip with these modalities and discusses the details of these techniques, particularly CT and MRI, that are pertinent to the orthopedic surgeon.

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